The focus of this project is on the delineation of the biochemical events involved in the activation of cells of the immune system, particularly the monocyte, with the objective of understanding the underlying mechanisms involved in the immunopathology of inflammatory diseases. Specific areas of interest include: 1) elucidation of the signal transduction events involved in the activation of monocytes as they relate to the production of arachidonic acid metabolites, monokines, and matrix metalloproteinases (MMP); 2) determination of the effect of defined biological mediators, such as lymphokines and microbial components, on the regulation of cytokine, eicosanoid and MMP production; 3) examination of specific extracellular matrix substrate-receptor interactions that may induce eicosanoid and metalloproteinase production; 4) In situ analysis of inflamed tissue to identify the cells involved in prostaglandin synthase and MMP production; and 5) the role of HIV infection and viral proteins on monocyte and immune function.